The present emphasis of this project is the study of host genetic determinants of sensitivity and resistance to induction of MAIDS by the replication defective virus termed BM5def MuLV. Differences in susceptibility to MAIDS among inbred strains of mice reflect the function of host genes, both within and outside the MHC complex, that may influence infection by and spread of the replication competent viruses that act as helper for spread of the defective virus genome or may act in primary control of the spread or activity of BM5def. Using LP-BM5 MuLV, which contains B-tropic helper MuLVs, for Fv-1(b) strains, mice of the H-2 haplotypes b, j, k, p, r and s were found to be moderately to highly sensitive while H-2(d) and H-2(a) strains were resistant. By testing mice with recombinant MHC complexes, resistance was mapped in association with class I molecules, and in some strains the d haplotype at the D-end of H-2 was implicated. In further tests of MHC Class I effects we have found that mutations at H-2D can render a resistant mouse sensitive, and mice of a resistant strain inoculated with LP-BM5 MuLV and then depleted of CD8+ T cells developed MAIDS and integration of the defective genome was demonstrated. In some resistant strains but not all, helper virus replication is suppressed, probably by effects of both MHC and non-MHC genes.